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Lymph node staging and radiotherapy contribute to gastric cancer outcomes

Adequate lymph node staging is critical to the appropriate management of gastric cancer, and radiotherapy appears to improve outcomes of patients even when lymph node staging is inadequate, according to findings from the National Cancer Data Base (NCDB).

In the U.S., where more extensive regional lymphadenectomy during gastrectomy has been widely adopted, studies investigating the value of adding radiotherapy to chemotherapy have yielded conflicting results.
Dr. Robert E. Roses and colleagues from the University of Pennsylvania Perelman School of Medicine, Philadelphia, used NCDB data on 3008 patients who underwent gastrectomy for gastric adenocarcinoma to compare the survival impact of adjuvant chemoradiotherapy (CRT) with that of chemotherapy alone.
Overall, mortality was 29% higher after chemotherapy alone than after CRT (p<0.001), according to the July 1 Annals of Surgery online report.

Increasing pathologic stage, lymph node positivity, and inadequate lymph node staging all strongly predicted risk-adjusted mortality.

In a propensity-matched comparison, median overall survival was significantly longer among 1869 CRT patients (36.1 months) than among 669 chemotherapy-alone patients (28.9 months).

Moreover, CRT patients had better 1-year (83.9%) and 5-year (40.2%) overall survival than their chemotherapy-alone counterparts (74.9% and 31.9%, respectively; p<0.001).

The survival benefit of CRT appeared to be greatest among patients receiving the least adequate lymph node staging, particularly (but not exclusively) among patients with node-positive disease.

"In summary, these data provide compelling evidence that adjuvant CRT should remain the standard of care adjuvant approach in the United States," the researchers concluded. "The addition of radiotherapy to regimens has a particularly strong association with improved survival in surgically understaged patients and those with node-positive disease."

"These data underscore the need for prospective studies examining the relative impact of radiotherapy on disease-specific survival in the United States and provide further rationale for improved surgical standardization," they added. "Not only is inadequate (lymph node staging) an independently poor prognosticator of gastric cancer outcomes in the United States, but it may also allow more rational selection of adjuvant therapy."

Dr. Daniele Marrelli, from the University of Siena's Unit of Surgical Oncology, Siena, Italy, told Reuters Health by email, "In my opinion, the extended (D2 or more) lymphadenectomy is a crucial step in gastric cancer treatment. The addition of chemoradiotherapy could in part attenuate the adverse effects of an inadequate lymph node dissection, but the survival curves of this study clearly indicate that the best long-term results are obtained when more than 30 lymph nodes are removed."

"The best results in terms of postoperative morbidity/mortality and long-term survival are reported in centers with a high volume of gastric cancer surgery and experienced with the D2 lymphadenectomy procedure," Dr. Marrelli said. "The chance of cure could be also increased with the addition of adjuvant or neoadjuvant therapies. In my opinion, gastric cancer needs a multimodal treatment, in line with the modern trends of the multidisciplinary approach, with the involvement of dedicated endoscopists, radiologists, pathologists, surgeons, oncologists, and radiotherapists. This is the only way to improve the therapeutic results of this aggressive and still fatal disease."
Dr. Marcel Verheij, from the Netherlands Cancer Institute, Amsterdam, the Netherlands, told Reuters Health by email, "The current data demonstrate the benefit from postoperative chemoradiation, even in patients who underwent adequate lymph node dissection, and confirm our conviction that postoperative chemoradiotherapy does not compensate for poor surgery, but adds to improved survival."

"Recently, the Dutch CRITICS trial has been closed and awaits its analysis," Dr. Verheij said. "This trial randomized between postoperative chemotherapy and postoperative chemoradiation after preoperative chemo and will provide further prospective data on this issue."

Dr. Dan G. Blazer III, from Duke University Medical Center, Durham, North Carolina, told Reuters Health by email, "It has long been known that patients in the United States frequently undergo insufficient lymphadenectomy in resected gastric cancer. Because gastric cancer remains a relatively rare malignancy in the United States, patients should be treated at centers where multidisciplinary discussion of these patients takes place -- multidisciplinary review includes medical oncology, radiation oncology, surgical pathology, radiology, and surgery. Surgical resection should be carried out by experienced, high-volume surgeons only after multidisciplinary discussion has taken place."

Dr. Blazer concluded, "As always, the most important advances in the management of patients with gastric cancer over the last 10-15 years have been realized in the context of high level, randomized controlled trials. We must continue to pursue answers to these complicated questions in this context."

Bron: Ann Surg 2015

06 August 2015

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